04906nas a2201489   4500000000100000000000100001008004100002260001200043653002400055653002600079653001600105653002000121100002300141700002300164700002500187700002000212700001500232700001900247700001200266700002200278700001300300700001500313700002000328700002000348700001400368700001800382700002100400700001900421700001800440700001600458700002000474700001800494700002300512700001800535700001500553700001800568700001800586700001800604700001700622700001500639700001800654700001900672700002500691700001500716700001600731700001800747700001700765700002000782700001900802700002300821700001300844700001700857700001500874700002000889700002200909700001800931700001800949700002400967700002000991700001801011700001701029700001901046700002801065700001901093700001601112700001701128700001701145700002101162700001701183700002101200700002001221700002101241700001701262700001901279700001901298700001801317700001701335700002101352700001901373700002001392700002401412700001901436700002201455700001801477700002201495700002101517700002601538700002201564700001701586700001801603700002001621700001901641700001701660700002101677700001801698700001501716700002801731700002301759700002001782700001601802700002101818700001401839700001701853700002001870700001801890700001701908700001301925700002601938700001801964700002301982700001702005700002202022700002002044700002102064700002102085700001902106700002402125700002202149700001802171700001502189245006202204856005502266300001402321490000702335520106002342022001403402       2024                            d  c2024-1210aAlzheimer's disease10aCellular neuroscience10aEpigenomics10aGene expression1 aMariano I. Gabitto1 aKyle J. Travaglini1 aVictoria M. Rachleff1 aEitan S. Kaplan1 aBrian Long1 aJeanelle Ariza1 aYi Ding1 aJoseph T. Mahoney1 aNick Dee1 aJeff Goldy1 aErica J. Melief1 aAnamika Agrawal1 aOmar Kana1 aXingjian Zhen1 aSamuel T. Barlow1 aKrissy Brouner1 aJazmin Campos1 aJohn Campos1 aAmbrose J. Carr1 aTamara Casper1 aRushil Chakrabarty1 aMichael Clark1 aJonah Cool1 aRachel Dalley1 aMartin Darvas1 aSong-Lin Ding1 aTim Dolbeare1 aTom Egdorf1 aLuke Esposito1 aRebecca Ferrer1 aLynn E. Fleckenstein1 aRohan Gala1 aAmanda Gary1 aEmily Gelfand1 aJessica Gloe1 aNathan Guilford1 aJunitta Guzman1 aDaniel Hirschstein1 aWindy Ho1 aMadison Hupp1 aTim Jarsky1 aNelson Johansen1 aBrian E. Kalmbach1 aLisa M. Keene1 aSarah Khawand1 aMitchell D. Kilgore1 aAmanda Kirkland1 aMichael Kunst1 aBrian R. Lee1 aMckaila Leytze1 aChristine L. Mac Donald1 aJocelin Malone1 aZoe Maltzer1 aNaomi Martin1 aRachel McCue1 aDelissa McMillen1 aGonzalo Mena1 aEmma Meyerdierks1 aKelly P. Meyers1 aTyler Mollenkopf1 aMark Montine1 aAmber L. Nolan1 aJulie K. Nyhus1 aPaul A. Olsen1 aMaiya Pacleb1 aChelsea M. Pagan1 aNicholas Peña1 aTrangthanh Pham1 aChristina Alice Pom1 aNadia Postupna1 aChristine Rimorin1 aAugustin Ruiz1 aGiuseppe A. Saldi1 aAimee M. Schantz1 aNadiya V. Shapovalova1 aStaci A. Sorensen1 aBrian Staats1 aMatt Sullivan1 aSusan M. Sunkin1 aCarol Thompson1 aMichael Tieu1 aJonathan T. Ting1 aAmy Torkelson1 aTracy Tran1 aNasmil J. Valera Cuevas1 aSarah Walling-Bell1 aMing-Qiang Wang1 aJack Waters1 aAngela M. Wilson1 aMing Xiao1 aDavid Haynor1 aNicole M. Gatto1 aSuman Jayadev1 aShoaib Mufti1 aLydia Ng1 aShubhabrata Mukherjee1 aPaul K. Crane1 aCaitlin S. Latimer1 aBoaz P. Levi1 aKimberly A. Smith1 aJennie L. Close1 aJeremy A. Miller1 aRebecca D. Hodge1 aEric B. Larson1 aThomas J. Grabowski1 aMichael Hawrylycz1 aC. Dirk Keene1 aEd S. Lein00aIntegrated multimodal cell atlas of Alzheimer’s disease  uhttps://www.nature.com/articles/s41593-024-01774-5  a2366-23830 v273 aAlzheimer’s disease (AD) is the leading cause of dementia in older adults. Although AD progression is characterized by stereotyped accumulation of proteinopathies, the affected cellular populations remain understudied. Here we use multiomics, spatial genomics and reference atlases from the BRAIN Initiative to study middle temporal gyrus cell types in 84 donors with varying AD pathologies. This cohort includes 33 male donors and 51 female donors, with an average age at time of death of 88 years. We used quantitative neuropathology to place donors along a disease pseudoprogression score. Pseudoprogression analysis revealed two disease phases: an early phase with a slow increase in pathology, presence of inflammatory microglia, reactive astrocytes, loss of somatostatin+ inhibitory neurons, and a remyelination response by oligodendrocyte precursor cells; and a later phase with exponential increase in pathology, loss of excitatory neurons and Pvalb+ and Vip+ inhibitory neuron subtypes. These findings were replicated in other major AD studies.  a1546-1726